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IndividualityMINCT03905993

Milieu Intérieur Collection - Genetic & Environmental Determinants Of Immune Phenotype Variance

An observational study of Individuality and Healthy Subjects, run by Institut Pasteur.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess the determinants of immunologic variance within the general healthy population. Read more about this study

Who is it for?
Ages 20 to 69 yearsHealthy volunteers can take part
Conditions the study is for
Individuality, Healthy Subjects
How many people
956 participants
Where
No sites listed yet
Study dates
17 Sep 2012to 8 Aug 2013
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 69 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Healthy adults subjects, aged from 20 to 69 years old, and whose ancestry for three generations was of Metropolitan French origin

Who may be able to join

  • Subjects considered as healthy by the investigator based on medical history, clinical examination, laboratory results and ECG (blood sampling for laboratory assessments and ECG were performed at V0 and only after signed informed consent).
  • Subjects who, according to the investigator, complied with the requirements of the protocol and were available for all scheduled visits at the investigational site.
  • Healthy male or female aged between 20 and 69 (included) years
  • Metropolitan French origin for 3 generations
  • 18.5 ≤BMI ≤ 32 kg/m²
  • Ability to give their informed consent in writing
  • Understanding of spoken and written French
  • Affiliated to the French social security or assimilated regimens

Who cannot join

  • Participation in another clinical study in the previous 3 months in which the subject had been exposed to an investigational product (pharmaceutical product or placebo or medical device) or concurrent participation in another clinical study during the study period
  • Relatedness to previously recruited individuals in the study cohort
  • Travel in (sub-)tropical countries within the previous 3 months
  • For women: pregnant or breastfeeding or intending to become pregnant or peri-menopausal*
  • Peri-menopausal women as defined by menstrual irregularity: either a change in the menstrual cycle length of more than seven days (early perimenopause) or two or more missed periods with an interval of 60 days or more between periods (late perimenopause) (Stages of Reproductive Aging Workshop, STRAW)
  • Any physical exercise within the previous 8 hours before study visits.
Show all 37Show fewer
  • Subjects following a special diet for medical reasons as prescribed by a GP or dietician (e.g. calorie restricted or weight-loss diet for significant overweight, cholesterol lowering diet or subjects suffering from any clinically diagnosed food allergy or intolerance)
  • Alcohol abuse (more than 50 g of pure ethanol per day: for example, more than 4 x 150 mL glasses of wine, more than 4 x 250 mL glasses of beer, more than 4 x 40 mL glasses of high alcohol content drinks)
  • Illicit drug use or substance abuse within 3 months prior to inclusion
  • Presence of evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to participate in the study satisfactorily.
  • Severe/chronic/recurrent pathological conditions, among them:
  • 10.1. Past or present diagnosed cancer, lymphoma, leukemia to the exception of:
  • Persons with a history of cancer who are disease-free without treatment for 5 years or more
  • Women who are disease free for 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen
  • Cutaneous or cervical basal cell carcinoma 10.2. Personal history of organ transplant 10.3. Congenital or acquired immune deficiency (any confirmed or suspected immunosuppressive or immunodeficient condition, including history of HIV infection) 10.4. Personal history of auto-immune diseases requiring or having previously required treatment (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sarcoidosis, Ankylosing Spondylitis, Autoimmune Hemolytic Anemia, Autoimmune Thrombocytopenic Purpura, Crohn's Disease, Psoriasis, Scleroderma, Wegener's Granulomatosis,Type I Diabetes, Thyroiditis,….) 10.5. Splenectomy 10.6. Acute or chronic, clinically significant, as determined by the investigator, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests 10.7. History of clinically significant, as determined by the investigator, neurological disorder or seizures 10.8. Infectious diseases:
  • Chronic infection (e.g. HIV, HBV, HCV…) or current acute infection or past acute infection based on investigator's judgment within the previous 3 months,
  • Presence of a rectal temperature ≥38.4°C, or axillary temperature ≥37.5°C, or intra-auricular temperature ≥38.4 °C, or buccal temperature ≥38°C on the scheduled date of inclusion,
  • Subject receiving (currently or in the last 3 months) antibiotics, intestinal, nasal or respiratory antiseptics.
  • 10.9. Severe High Blood Pressure defined as systolic BP≥160 mmHg and/or diastolic BP≥100 mmHg (AHA stage 2 HBP). Treated and controlled HBP is allowed.
  • 10.10. Type II diabetes mellitus requiring treatment with any medication. Diabetes mellitus treated by exercise and diet control only is permitted.
  • 10.11. Chronic renal impairment as defined by Renal Insufficiency: GFR<60 mL/min/1.73 m² (National Kidney Foundation (2002).
  • 10.12. Chronic bone disease as treated by biphophonates. 10.13. Treated depression or any evidence of overt depressive episode during medical examination and interview.
  • 10.14. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin or antiplatelet medications within 2 months preceding inclusion.
  • 10.15. Dermatologic conditions: any current dermatological disorder that is severe enough to prevent the skin biopsy (e.g. eczema, psoriasis, acute or chronic dermatitis).
  • 10.16. Severe acute/chronic allergy
  • Severe Asthma defined as asthma requiring a combination of two or more controller therapies (e.g. medium or high dose inhaled glucocorticosteroid and long-acting inhaled beta-2 agonist) or requiring oral glucocorticosteroids (GINA).
  • Severe food allergy, as defined by history of giant urticaria, Quincke edema or anaphylactic shock,
  • Severe insect bite allergy with history of giant urticaria, Quincke edema or anaphylactic shock,
  • Atopic dermatitis treated with medication.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to the inclusion. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for > 2 weeks (inhaled and topical steroids allowed)
  • Chronic administration of NSAIDs, including aspirin: prolonged intake (> 2 weeks) within 6 months before study or any intake within the 7 days preceding skin biopsy [exception for low dose aspirin: maximum 250mg/daily, see 8.1]
  • Receipt of any vaccination 3 months before the inclusion or planning to receive any vaccination during the study
  • Receipt of blood products or immunoglobulins within 3 months prior the inclusion or planning to receive blood products or immunoglobulins during the study
  • Hemoglobin measurement less than 10.0 g/dL for women and less than 11.5 g/dL for men
  • Platelet count less than 120.000/mm3
  • ALAT and/or ASAT > 3 times the upper limit of the norm (ULN)
  • Allergy to lidocaine

About this study

Official title: Genetic & Environmental Determinants Of Immune Phenotype Variance: Establishing A Path Towards Personalized Medicine

The purpose of this study is to assess the determinants of immunologic variance within the general healthy population.

Read the detailed description

Susceptibility to infections, disease severity, and response to medical therapies and vaccines are highly variable from one individual to another. While the question of variance in human populations continues to be a focal point of scientific research, medical practices and public health policies typically take a 'one size fits all' model to disease management and drug development.

Individual heterogeneity in the immune response can have an enormous impact on the likelihood to respond to therapy or the development of side effects secondary to vaccine administration. Because of the complexity of immune responses in the individual and within the population, it has not been possible thus far to define the parameters (genetic or environmental) that constitute a healthy immune system and its natural occurring variability.

Efforts to restore the 'personal' in medical care are the current challenge, and the driving vision of the project, to which the current study belongs.

In order to realize the promise of personalized medicine, an in-depth understanding of the determinants of heterogeneity in host response to stress is required. The Milieu Interieur cohort was established to address these questions through a population systems immunology approach.

Keywords
Immune response, Immune System, genotype-to-phenotype association, genetic variability, reference-based population

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03905993
Study groupRoleWhat they receive
Experimental: unique group.At V0: 1238 subjects were screened At V1: 1012 subjects (12 later withdrew) gave the following samples: blood, nasal swab,stool. 323 subjects among 1000 gave one additional sample (Skin Biopsy) At V2: 504 subjects came at V2 to perform blood, nasal swab and stool samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Identify genetic associations with immune response variability

    Genome wide associations studies that combine whole genome genotyping data sets with immune response phenotypes to identify genetic regulators of immune function. These studies will be later completed with data from whole genome sequencing for more detailed genetic analysis.

    Measured: 2024

Secondary outcomes (1)

  1. Identify environmental associations with immune response variability

    Association of whole metagenomic data sets generated from fecal samples that reflect environmental exposures with immune response phenotypes.

    Measured: 2026

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2019
  2. Study start17 Sep 2012
  3. Primary completion8 Aug 2013
  4. Study completion8 Aug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Cross-sectional
Enrolment
956 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03905993
Sponsor's protocol ID
2017-070
Other IDs
ID-RCB : 2018-A00861-54, 10-LABX-0069
Acronym
MI
Status last verified
Apr 2019
First submitted
4 Apr 2019
Last updated
20 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Milieu Intérieur clinical data (CRF) have already been collected, and upon publication in peer reviewed journals certain biological data sets will be deposited in secure data warehouses to allow access for scientific research use only. All MI data sets are completely pseudo-anonymized (donors' identity is replaced with a unique MI number). Of the 1,000 subjects enrolled in the MI study, 956 have consented for their data to used outside the consortium for scientific research use only. This usage in approved scientific collaborations is reviewed by the Milieu Interieur data and sample access committee and also covers the deposit of pseudo-anonymized data sets in centrally controlled data repositories. All IPD that underlie results in peer reviewed publications may be shared for scientific collaborations following a request and review by the Milieu Interieur data and sample access committee.

Publications

  • Patin E, Hasan M, Bergstedt J, Rouilly V, Libri V, Urrutia A, Alanio C, Scepanovic P, Hammer C, Jonsson F, Beitz B, Quach H, Lim YW, Hunkapiller J, Zepeda M, Green C, Piasecka B, Leloup C, Rogge L, Huetz F, Peguillet I, Lantz O, Fontes M, Di Santo JP, Thomas S, Fellay J, Duffy D, Quintana-Murci L, Albert ML; Milieu Interieur Consortium. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nat Immunol. 2018 Mar;19(3):302-314. doi: 10.1038/s41590-018-0049-7. Epub 2018 Feb 23.

    PubMed 29476184

  • Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, Bergstedt J, Charbit B, Rouilly V, MacPherson CR, Hasan M, Albaud B, Gentien D, Fellay J, Albert ML, Quintana-Murci L; Milieu Interieur Consortium. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E488-E497. doi: 10.1073/pnas.1714765115. Epub 2017 Dec 27.

    PubMed 29282317

  • Thomas S, Rouilly V, Patin E, Alanio C, Dubois A, Delval C, Marquier LG, Fauchoux N, Sayegrih S, Vray M, Duffy D, Quintana-Murci L, Albert ML; Milieu Interieur Consortium. The Milieu Interieur study - an integrative approach for study of human immunological variance. Clin Immunol. 2015 Apr;157(2):277-93. doi: 10.1016/j.clim.2014.12.004. Epub 2015 Jan 3.

    PubMed 25562703

  • Clave E, Araujo IL, Alanio C, Patin E, Bergstedt J, Urrutia A, Lopez-Lastra S, Li Y, Charbit B, MacPherson CR, Hasan M, Melo-Lima BL, Douay C, Saut N, Germain M, Tregouet DA, Morange PE, Fontes M, Duffy D, Di Santo JP, Quintana-Murci L, Albert ML, Toubert A; Milieu Interieur Consortium. Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus. Sci Transl Med. 2018 Sep 5;10(457):eaao2966. doi: 10.1126/scitranslmed.aao2966.

    PubMed 30185651

Questions about this trial

What is this clinical trial studying?

An observational study of Individuality and Healthy Subjects, run by Institut Pasteur.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Identify genetic associations with immune response variability (time frame: 2024). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03905993, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2022.

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